Scientists have discovered a T-cell receptor that has proven effective in targeting a variety of cancers in mice and in human cells within the lab.
Image Credit: Meletios Verras/Shutterstock.com
These early findings predict that the discovery could facilitate the development of a new T-cell cancer therapy that would target and destroy a range of cancer types without the limitations of current T-cell therapies that require tailoring to the patient.
CRISPR-Cas9 Screening identifies new T-cell
A research team led by scientists at Cardiff University in Wales conducted a new study where they used a genome-wide CRISPR-Cas9 screening approach to search for genes that are vital to the recognition of target cells. Their efforts led them to discover the receptor molecule, known as MR1. Preliminary lab tests have shown that the receptor molecule is effective at attacking a wide range of cancers, although testing in living human patients has yet to take place. However, at this stage, the discovery looks promising in its capacity at producing an important advancement in T-cell therapies.
Potential “one-size-fits-all” therapy
The body’s immune system utilizes T-cells to protect it from foreign invaders and defective cells, such as viruses or cancer, preventing the initiation of disease or infection. To do this, the T-cells are programmed to seek out cells it views as a threat, engulfing, and destroying them.
T-cell cancer therapy exploits the encoded behavior of T-cells, with current methods most commonly targeting the Chimeric Antigen Receptor T-cells (CAR-T) which are manipulated, so they orient themselves specifically towards tumorous cells.
However, whilst this emerging field of medicine has so far proven to be successful, it is not without its drawbacks. Firstly, the therapy must be adjusted to suit each patient. This is because the T-cell receptor known as human leukocyte antigen (HLA) which allows T-cells to detect cancer cells is not uniform across different people.
Therefore, for T-cell therapy to work, scientists must first obtain T-cells from the patients’ blood and augment them so they can specifically target and destroy tumorous cells. Also, this current form of T-cell therapy is limited in its effectiveness, having only been proved successful at targeting specific cancer types.
This new discovery will address these limitations, potentially helping deliver an improved T-cell cancer therapy that attacks a wide variety of cancers without the need for tailoring the treatment. Potentially, the discovery could open the door to a “one-size-fits-all” therapy.
The identification of the MR1 receptor molecule is exciting because like HLA, it can target and destroy cancer cells, however, unlike HLA is does not vary between people, and therefore therapies utilizing MR1 would not need personalization.
Further to this, lab studies have shown MR1’s effectiveness at attacking a wide range of cancers, including lung, melanoma, leukemia, colon, breast, prostate, bone and ovarian, which do not have a HLA in common. These results are positive in that they suggest the possibility of developing a T-cell therapy that could be used across the human population, targeting a potentially wide range of cancers.
However, scientists continue to emphasize that human trials need to be conducted before the potential new T-cell therapy can truly be considered. So far MR1’s effectiveness has only been proven in mice, and in human cells in the lab, not in living humans.
Image Credit: Cardiff University
Human trials will shortly begin
The next steps will be for the researchers to test whether the promising activity of MR1 can be replicated in humans. In addition to running clinical trials, which are expected to take place as early as this year, scientists will also be investigating how many types of cancer can be targeted with MR1, and what the underlying mechanisms of its effectiveness are.
If the effectiveness of MR1 can be replaced in human trials, then this would signify the beginning of significant advancement in T-cell cancer therapy.
Crowther, M.D., Dolton, G., Legut, M. et al. Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nat Immunol (2020) doi:10.1038/s41590-019-0578-8